Enhancing CAR-NK persistence to unlock its full therapeutic potentials

Chimeric Antigen Receptor-Natural Killer Cell (CAR-NK) is a promising next-generation immunotherapy. Persistence of CAR-NK cell therapy is considered a key hurdle limiting its full therapeutic potential. This review highlighted the causes of poor CAR-NK persistence and summarized strategies developed to improve CAR-NK persistence in both hematologic malignancies and solid tumors. These strategies included cytokine and cytokine signaling mediated strategies; optimization of NK cell source and CAR design; intrinsic and extrinsic checkpoint disruption and metabolic reprogramming; and lymphodepletion, alloevasion and fratricide evasion strategies. Multiple strategies that aim at improving in vivo persistence should prove useful in enhancing therapeutic efficacy of CAR-NK.